A multisegmented effort, with extensive overlaps, is to be applied to a selected segment of blood coagulation as it relates to itself and tissue cells. The inhibitor of blood coagulation called autoprothrombin II-A is to be isolated by methods recently perfected. The origin or mother substance(s) is to be determined. Further studies of its effects on coagulation and fibrinolysis are to be carried out. The reactions of Factor Xa with purified antithrombin III are being studied at the level of molecular biology. Purification of Factor XI is being perfected, and the effects of the product on the activation of Factor IX are programed for study. By using the electron microscope the molecular particles of the following purified proteins are to be studied: whole lung thromboplastin, prothrombin, O fragment of prothrombin, PR fragment of prothrombin, Factor X, prethrombin, antithrombin III, fibrinogen and Ac-globulin. These same substances are being studied for immunological responses. The protein portion of brain thromboplastin, and lung thromboplastin has been purified and preliminary studies of the protein structure are being undertaken. Cultured endothelial cells, and endothelial cells are to be studied with respect to responses to enzymes and other substances with use of scanning E.M. Modification of endothelial cell-platelet interaction capability is under study. Studies related to in vivo thrombosis and hemostasis are being done in terms of a rat-tail hemostatic model and a dog extracorporeal shunt-and-sieve model.